Article
Oncology
Migle Gabrielaite, Mathias Husted Torp, Malthe Sebro Rasmussen, Sergio Andreu-Sanchez, Filipe Garrett Vieira, Christina Bligaard Pedersen, Savvas Kinalis, Majbritt Busk Madsen, Miyako Kodama, Guel Sude Demircan, Arman Simonyan, Christina Westmose Yde, Lars Ronn Olsen, Rasmus L. Marvig, Olga ostrup, Maria Rossing, Finn Cilius Nielsen, Ole Winther, Frederik Otzen Bagger
Summary: Copy-number variations (CNVs) have significant clinical implications for various diseases and cancers, but detecting relevant CNVs accurately remains challenging. Our study found diverse performance levels among different CNV calling tools, suggesting that combining the best tools could be a potential solution.
Article
Biology
Milovan Suvakov, Arijit Panda, Colin Diesh, Ian Holmes, Alexej Abyzov
Summary: CNVpytor is an extension of CNVnator that improves performance and functionality, allowing for filtering, annotation, and merging of CNV calls across multiple samples. Its modular architecture enables use in shared and cloud environments, and data can be exported to JBrowse for visualization and analysis.
Article
Biochemistry & Molecular Biology
Ho Jang, Chang-Min Choi, Seung-Hyeun Lee, Sungyong Lee, Mi-Kyung Jeong
Summary: Plasma cfDNA sequencing data has potential for detecting CNAs in cancer patients. The detection performance can be improved by suppressing the RC patterns.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Pourya Davoudi, Duy Ngoc Do, Bruce Rathgeber, Stefanie M. Colombo, Mehdi Sargolzaei, Graham Plastow, Zhiquan Wang, Karim Karimi, Guoyu Hu, Shafagh Valipour, Younes Miar
Summary: This study presents the first genome-wide CNV analysis of American mink, using whole-genome sequence data from 100 individuals. The results suggest potential links between CNVs and mink behavior, fur quality, and immune response.
Article
Oncology
Tomohiro Tanaka, Yasushi Goto, Masafumi Horie, Ken Masuda, Yuki Shinno, Yuji Matsumoto, Yusuke Okuma, Tatsuya Yoshida, Hidehito Horinouchi, Noriko Motoi, Yasushi Yatabe, Shunichi Watanabe, Noboru Yamamoto, Yuichiro Ohe
Summary: This study investigates somatic single-nucleotide variants or copy number variations in exceptional responders to pemetrexed treatment using whole-exome sequencing. The results suggest that exceptional responders may have a higher number of copy number variations. This study provides important insights into the mechanism of exceptional responses and contributes to genomic findings on thymomas and chemosensitivity.
Article
Biochemical Research Methods
Xinping Fan, Guanghao Luo, Yu S. Huang
Summary: This study presents Accucopy, a method for inferring total copy numbers (TCNs) and allele-specific copy numbers (ASCNs) from challenging low-purity and low-coverage tumor samples. Accucopy utilizes robust statistical techniques and models such as the tiered Gaussian mixture model, expectation-maximization algorithm, and sparse Bayesian learning, outperforming other methods in simulated and real sequencing samples.
BMC BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Xiaotong Li, Sushant Kumar, Arif Harmanci, Shantao Li, Robert R. Kitchen, Yan Zhang, Vikram B. Wali, Sangeetha M. Reddy, Wendy A. Woodward, James M. Reuben, Joel Rozowsky, Christos Hatzis, Naoto T. Ueno, Savitri Krishnamurthy, Lajos Pusztai, Mark Gerstein
Summary: Whole-genome sequencing of inflammatory breast cancer (IBC) shows similarities in genomic architecture to non-IBC, with no unique genomic alterations shared specifically in IBCs. However, subtle genomic differences were observed, including germline alterations in TGF beta pathway genes and somatic mutations in the MAST2 kinase that could potentially serve as therapeutic targets.
Article
Oncology
Renaud Sabatier, Severine Garnier, Arnaud Guille, Nadine Carbuccia, Jihane Pakradouni, Jose Adelaide, Magali Provansal, Maria Cappiello, Frederique Rousseau, Max Chaffanet, Daniel Birnbaum, Emilie Mamessier, Anthony Goncalves, Francois Bertucci
Summary: This study evaluated the genomic characteristics of recurrent heavily pre-treated ovarian carcinoma (OvC) and found that ctDNA characteristics were associated with prognosis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Neurosciences
Tiejia Jiang, Jia Gao, Lihua Jiang, Lu Xu, Congying Zhao, Xiaojun Su, Yaping Shen, Weiyue Gu, Xiaohong Kong, Ying Yang, Feng Gao
Summary: The study found that trio-whole exome sequencing can identify potentially pathogenic or likely pathogenic gene variants in pediatric patients with epilepsy, leading to better management and treatment strategies. The research also discovered new genes not previously associated with epilepsy.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Endocrinology & Metabolism
Lei Li, Qixuan Sheng, Huajin Zeng, Wei Li, Qiang Wang, Guanjun Ma, Xinyun Xu, Ming Qiu, Wei Zhang, Chengxiang Shan
Summary: This study provides a comprehensive analysis of the genetic characteristics of hyperplastic parathyroids in THPT, finding multiple driver mutations and enriched pathways involved in the development and progression of the disease.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemical Research Methods
Dayne L. Filer, Fengshen Kuo, Alicia T. Brandt, Christian R. Tilley, Piotr A. Mieczkowski, Jonathan S. Berg, Kimberly Robasky, Yun Li, Chris Bizon, Jeffery L. Tilson, Bradford C. Powell, Darius M. Bost, Clark D. Jeffries, Kirk C. Wilhelmsen
Summary: The introduction of multiplexed exome capture reduces variance and improves CNV detection through the novel mcCNV algorithm. This method, agnostic to prior information, demonstrates a favorable false discovery rate compared to ExomeDepth in simulation studies. The benefits of this approach include not requiring a database of reference samples and not needing prior information about variant prevalence or size.
BMC BIOINFORMATICS
(2021)
Article
Genetics & Heredity
Bo Ye, Xia Tang, Shixiu Liao, Keyue Ding
Summary: CLAMMS and CODEX2 algorithms outperformed others in accurately identifying gCNVs for genetic diagnosis.
Article
Oncology
Pattapon Kunadirek, Natthaya Chuaypen, Piroon Jenjaroenpun, Thidathip Wongsurawat, Nutcha Pinjaroen, Pongserath Sirichindakul, Intawat Nookaew, Pisit Tangkijvanich
Summary: The study demonstrated the utility of using whole-exome sequencing of cfDNA to define somatic mutation profiles of HCC in Thai patients, revealing the association of HRNR and TTN mutations in cfDNA with shorter overall survival. The findings suggest that cfDNA could serve as a useful biomarker for diagnosis and prognosis in Thai HCC patients, with potential applications in onsite clinical detection/monitoring of HCC using pocket-sized sequencers.
Article
Oncology
Xin Liao, Xuyang Xia, Wei Su, Huayun Yan, Yingfang Ma, Lian Xu, Han Luo, Wanting Liu, Dandan Yin, Wei-Han Zhang, Hai-Ning Chen, Yiqi Deng, Zhixiang Ren, Zehui Yu, Fei Liao, Keling Chen, Minyuan Cao, Yiguan Zhang, Wei Zhang, Wei Wang, Jun-Ning Zhao, Heng Xu, Yang Shu
Summary: The study investigated the genomic alterations and prognostic value of gastric-type cervical adenocarcinoma (GCA) in Chinese patients. Mutations were commonly observed in GCA-related driver genes, and the alteration of APOBEC3B was found to be associated with favorable prognosis.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Oncology
Ji-Qing Chen, Lucas A. Salas, John K. Wiencke, Devin C. Koestler, Annette M. Molinaro, Angeline S. Andrew, John D. Seigne, Margaret R. Karagas, Karl T. Kelsey, Brock C. Christensen
Summary: This study used DNA methylation profiles and cell type analysis to identify that increasing CD4T and CD8T cell proportions were associated with a decreased hazard of tumor recurrence or death in NMIBC patients, while increasing monocyte proportion and mdNLR were associated with an increased hazard. Additionally, 2528 CpGs associated with tumor recurrence or death were identified through epigenome-wide association study.
CLINICAL EPIGENETICS
(2022)
Article
Pediatrics
Jesse M. Tehrani, Elizabeth Kennedy, Pei Wen Tung, Amber Burt, Karen Hermetz, Tracy Punshon, Brian P. Jackson, Ke Hao, Jia Chen, Margaret R. Karagas, Devin C. Koestler, Barry Lester, Carmen J. Marsit
Summary: The study found that prenatal exposure to cadmium may affect the expression of placental microRNAs, which target genes involved in nervous system development and are associated with abnormal neurobehavioral outcomes in newborns.
PEDIATRIC RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
Jesse M. Tehrani, Elizabeth M. Kennedy, Fu-Ying Tian, Todd M. Everson, Maya Deyssenroth, Amber Burt, Karen Hermetz, Ke Hao, Jia Chen, Devin C. Koestler, Carmen J. Marsit
Summary: Cardiovascular disease is a major cause of death in the United States, and the rate of maternal mortality is high. Research indicates that the expression of placental microRNAs is linked to maternal cardiometabolic health and may contribute to the developmental programming of chronic disease in offspring.
JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
(2023)
Article
Pediatrics
Elizabeth M. Kennedy, Karen Hermetz, Amber Burt, Dong Pei, Devin C. Koestler, Ke Hao, Jia Chen, Diane Gilbert-Diamond, Usha Ramakrishnan, Margaret R. Karagas, Carmen J. Marsit
Summary: Placental microRNAs are associated with early childhood growth trajectory and play a role in regulating placental cellular dynamics, impacting infant growth beyond birth.
PEDIATRIC RESEARCH
(2023)
Article
Chemistry, Analytical
Mengjia Hu, Virginia Brown, Joshua M. Jackson, Harshani Wijerathne, Harsh Pathak, Devin C. Koestler, Emily Nissen, Mateusz L. Hupert, Rolf Muller, Andrew K. Godwin, Malgorzata A. Witek, Steven A. Soper
Summary: Extracellular vesicles (EVs) have the potential to be used as a minimally invasive liquid biopsy marker for precision medicine, as they carry RNA cargo associated with the cell-of-origin. Researchers have developed an EV microfluidic affinity purification (EV-MAP) chip, made from plastic for high-scale production, which can isolate EV subpopulations. They demonstrated the utility of this chip in molecular subtyping breast cancer patients, isolating two subpopulations of EVs that better recapitulate the tumor microenvironment. The EV-MAP provided high recovery and specificity based on exosomal mRNA and PCR results, and the EV subpopulations showed potential for prognostication using the PAM50 test.
ANALYTICAL CHEMISTRY
(2023)
Article
Oncology
Julia Debertin, Flavia Teles, Lynn M. Martin, Jiayun Lu, Devin C. Koestler, Karl T. Kelsey, James D. Beck, Elizabeth A. Platz, Dominique S. Michaud
Summary: The study aimed to investigate the association between antibodies to oral bacteria and the risk of colon cancer. A nested case-control study was conducted using the CLUE I cohort, and it was found that certain levels of oral bacterial antibodies were inversely associated with colon cancer risk, while one antibody showed a positive association. This suggests that a strong adaptive immune response may be associated with a lower risk of colon cancer.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Article
Genetics & Heredity
Shelby Bell-Glenn, Lucas A. Salas, Annette M. Molinaro, Rondi A. Butler, Brock C. Christensen, Karl T. Kelsey, John K. Wiencke, Devin C. Koestler
Summary: DNA methylation (DNAm)-based cell mixture deconvolution (CMD) is important in epigenome-wide association studies, but the detection limits and uncertainty quantification of DNAm-based CMD have not been determined. This study describes analytical frameworks for determining the detection limits and quantifying the uncertainty of DNAm-based CMD, which may improve the rigor, reproducibility, and replicability of epigenome-wide association studies involving CMD.
Article
Oncology
Emily Nissen, Alexander Reiner, Simin Liu, Robert B. Wallace, Annette M. Molinaro, Lucas A. Salas, Brock C. Christensen, John K. Wiencke, Devin C. Koestler, Karl T. Kelsey
Summary: In the past decade, DNAm-based deconvolution methods have been developed to estimate the proportions of leukocytes in peripheral blood using cell-specific DNAm markers. This study provides reference ranges for immune populations in a group of post-menopausal American women.
CLINICAL EPIGENETICS
(2023)
Article
Neurosciences
Ze Zhang, John K. Wiencke, Karl T. Kelsey, Devin C. Koestler, Annette M. Molinaro, Steven C. Pike, Prasoona Karra, Brock C. Christensen, Lucas A. Salas
Summary: Studying the composition of brain cells and their association with neurological conditions is important for understanding brain-related pathophysiology and neuroscience. A DNA methylation-based deconvolution method can be used to identify different types of brain cells. Our study demonstrates the potential utility of this method in normal and diseased brain tissues, including Alzheimer's disease, autism, Huntington's disease, epilepsy, and schizophrenia. This method can accelerate the understanding of cellular composition and cell-type-specific epigenetic states in normal and diseased brain tissues.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Oncology
Nana K. Ampomah, Flavia Teles, Lynn M. Martin, Jiayun Lu, Devin C. Koestler, Karl T. Kelsey, James D. Beck, Elizabeth A. Platz, Dominique S. Michaud
Summary: Oral health is a crucial indicator of overall health and quality of life. New evidence suggests that oral diseases such as periodontitis may increase the risk of various cancers, including lung, colorectal, and pancreatic cancers.
JNCI CANCER SPECTRUM
(2023)
Article
Oncology
Ji-Qing Chen, Lucas A. Salas, John K. Wiencke, Devin C. Koestler, Annette M. Molinaro, Angeline S. Andrew, John D. Seigne, Margaret R. Karagas, Karl T. Kelsey, Brock C. Christensen
Summary: This study found associations between specific immune cell subtypes, age acceleration, and bladder cancer outcomes. These findings provide important prognostic information for the management of bladder cancer recurrence and survival.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2023)
Article
Dentistry, Oral Surgery & Medicine
Naisi Zhao, Flavia Teles, Jiayun Lu, Devin C. Koestler, James Beck, Eric Boerwinkle, Jan Bressler, Karl T. Kelsey, Elizabeth A. Platz, Dominique S. Michaud
Summary: This study investigated individual susceptibility to periodontitis by conducting an epigenome-wide association study using peripheral blood. The results showed that epigenetic variations in ZPF57 and HOXA4 were significantly associated with periodontitis.
JOURNAL OF CLINICAL PERIODONTOLOGY
(2023)
Article
Computer Science, Artificial Intelligence
Vincent Schilling, Peter Beyerlein, Jeremy Chien
Summary: In this study, a machine learning approach was proposed to predict the outcomes and platinum resistance status of ovarian cancer patients using gene expression data. Multiple genes that correlated with patient outcomes and platinum resistance were identified and validated.
Article
Biochemistry & Molecular Biology
Bo Zhang, Jianghua He, Jinxiang Hu, Prabhakar Chalise, Devin C. Koestler
Summary: Component-wise Sparse Mixture Regression (CSMR) is a promising regression-based clustering method for detecting heterogeneous relationships. However, it can yield inconsistent results in high-dimensional data due to limitations in feature selection. We explored different regularized regression methods within the CSMR framework and found that substituting Adaptive-Lasso improved the clustering accuracy and internal consistency, even in high-dimensional scenarios.
STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Dominique S. Michaud, Mei Chung, Naisi Zhao, Devin C. Koestler, Jiayun Lu, Elizabeth A. Platz, Karl T. Kelsey
Summary: This study investigated the association between three different biological age acceleration measures and risk of lung cancer, and found no significant association between them.
